Jacaric acid, a linolenic acid isomer with a conjugated triene system, has a strong antitumor effect in vitro and in vivo.

In this study, we compared the cytotoxic effects of natural conjugated linolenic acids (CLnAs) on human adenocarcinoma cells (DLD-1) in vitro, with the goal of finding CLnA isomers with strong cytotoxic effects. The antitumor effect of the CLnA with the strongest cytotoxic effect was then examined in mice. The results showed that all CLnA isomers have strong cytotoxic effects on DLD-1 cells, with jacaric acid (JA) having the strongest effect. Examination of the mechanism of cell death showed that CLnAs induce apoptosis in DLD-1 cells via lipid peroxidation. The intracellular levels of incorporated CLnAs were measured to examine the reason for differences in cytotoxic effects. These results showed that JA was taken into cells efficiently. Collectively, these results suggest that the cytotoxic effect of CLnAs is dependent on intracellular incorporation and induction of apoptosis via lipid peroxidation. JA also had a strong preventive antitumor effect in vivo in nude mice into which DLD-1 cells were transplanted. These results suggest that JA can be used as a dietary constituent for prevention of cancer.

Induction of apoptotic cell death in HL-60 cells by jacaranda seed oil derived fatty acids.

Various fatty acids are attracting considerable interest for their anticancer effects. Among them, fatty acids containing conjugated double bonds show one of the most potent cytotoxic effects on cancer cells. Here, we focused on the cancer cell killing activity of jacaranda seed oil. The seed oil of jacaranda harvested from Miyazaki in Japan contained 30.9% cis-8, trans-10, cis-12 octadecatrienoic acid, called jacaric acid (JA). Fatty acid prepared from this oil (JFA) and JA strongly induced cell death in human leukemia HL-60 cells. On the other hand, linoleic acid and trans-10, cis-12 conjugated linoleic acid (<10 µM) did not affect cell proliferation and viability. An increase in the sub-G1 population and internucleosomal fragmentation of DNA was observed in JA- and JFA-treated cells, indicating induction of apoptotic cell death. Finally, the cytotoxic effects of JA and JFA were completely abolished by α-tocopherol. Taken together, these data suggest that jacaranda seed oil has potent apoptotic activity in HL-60 cells through induction of oxidative stress.

jacaric acid, a linolenic acid isomer with a conjugated triene system, reduces stearoyl-CoA desaturase expression in liver of mice.

Conjugated fatty acid is a collective term used for fatty acids with conjugated double bond systems. Seed oils from certain plants include conjugated linolenic acids, which have a conjugated triene system and are geometrical and positional isomers of α-linolenic acid. One of these isomers, jacaric acid (JA, 8c, 10t, 12c-18:3), has not been examined widely. Therefore, we investigated the absorption and metabolism of JA in normal animals (ICR mice). An oral dose of JA of 5 mg/day for 1 week had no effects on body weight, food intake and tissue weight of mice. JA was detected in the serum, kidney, liver, lung and epididymal white adipose tissue. Analysis of the fatty acid composition in liver and white adipose tissue showed a tendency to increase levels of saturated fatty acids (SFAs) such as palmitic acid (16:0) and stearic acid (18:0) and to decrease levels of monounsaturated fatty acids (MUFAs) such as palmitoleic acid (16:1) and oleic acid (18:1). Thus, JA treatment decreased the desaturation index (16:1/16:0, 18:1/18:0) in liver and white adipose tissue. This index is used as an indicator of the activity of stearoyl coenzyme A desaturase (SCD), an endoplasmic reticulum enzyme that catalyzes the biosynthesis of MUFAs from SFAs. The change in this index indicates that JA inhibited SCD activity in ICR mice, and further experiments showed that JA also decreased the expression level of SCD-1 mRNA. Inhibition of SCD activity may have anti-obesity and anti-diabetes effects, and therefore the findings in this study suggest that JA may be effective for preventing obesity and diabetes.